Frozen sections have been routinely used from tissue biopsy for diagnostic purposes for many years but pathologists report difficulty in analyzing any type of frozen sections from tissues containing vesicles such as epidermal, liver, lymph nodal, testicular or intestinal tissue because of artifacts created by existing freezing techniques. It is the goal of this proposal to develop an instrument which will eliminate these artifacts using high hydrostatic pressure. During phase I it is expected that the basic instrument and techniques for freezing the tissue using high pressure will be developed. Using high pressure while decreasing the temperature will cause a freezing point depression to occur; thus at low temperature, when pressure is released freezing will occur spontaneously throughout the sample. Freezing under these conditions will result in the formation of extremely small crystals and avoid the large crystals which give rise to "freezing artifacts." Such tissue will then be sectioned in the cryostat and evaluated microscopically. Phase I will be concluded when the prototype has been built, tested and resultant frozen sections evaluated. Phase II will involve the development of an automated instrument based on the prototype to market a unit for the medical and scientific community.